Basophil-derived IL-4 promotes cutaneous Staphylococcus aureus infection
| Autor: | Sonal Singh, Frank Brombacher, Lloyd S. Miller, Alexander R. Horswill, Raif S. Geha, Jennifer Kane, Hajime Karasuyama, Daniel Sen Hoi Wong, Mrinmoy Das, Maria Strakosha, Juan Manuel Leyva-Castillo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Chemokine
Immunology Basophil Skin infection medicine.disease_cause Mice Immune system Bacterial infections medicine Interleukin 23 Animals Humans Interleukin 4 Innate immunity Infectious disease Innate immune system biology business.industry General Medicine Staphylococcal Infections medicine.disease Immunity Innate Basophils medicine.anatomical_structure Staphylococcus aureus biology.protein Staphylococcal Skin Infections Interleukin-4 business Research Article |
| Zdroj: | JCI Insight |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.149953 |
| Popis: | Superficial cutaneous Staphylococcus aureus (S. aureus) infection in humans can lead to soft tissue infection, an important cause of morbidity and mortality. IL-17A production by skin TCRγδ+ cells in response to IL-1 and IL-23 produced by epithelial and immune cells is important for restraining S. aureus skin infection. How S. aureus evades this cutaneous innate immune response to establish infection is not clear. Here we show that mechanical injury of mouse skin by tape stripping predisposed mice to superficial skin infection with S. aureus. Topical application of S. aureus to tape-stripped skin caused cutaneous influx of basophils and increased Il4 expression. This basophil-derived IL-4 inhibited cutaneous IL-17A production by TCRγδ+ cells and promoted S. aureus infection of tape-stripped skin. We demonstrate that IL-4 acted on multiple checkpoints that suppress the cutaneous IL-17A response. It reduced Il1 and Il23 expression by keratinocytes, inhibited IL-1+IL-23-driven IL-17A production by TCRγδ+ cells, and impaired IL-17A-driven induction of neutrophil-attracting chemokines by keratinocytes. IL-4 receptor blockade is shown to promote Il17a expression and enhance bacterial clearance in tape-stripped mouse skin exposed to S. aureus, suggesting that it could serve as a therapeutic approach to prevent skin and soft tissue infection. |
| Databáze: | OpenAIRE |
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